TY - JOUR A1 - Brumberg, Joachim A1 - Küsters, Sebastian A1 - Al-Momani, Ehab A1 - Marotta, Giorgio A1 - Cosgrove, Kelly P. A1 - van Dyck, Christopher H. A1 - Herrmann, Ken A1 - Homola, György A. A1 - Pezzoli, Gianni A1 - Buck, Andreas K. A1 - Volkmann, Jens A1 - Samnick, Samuel A1 - Isaias, Ioannis U. T1 - Cholinergic activity and levodopa-induced dyskinesia: a multitracer molecular imaging study JF - Annals of Clinical and Translational Neurology N2 - Objective: To investigate the association between levodopa‐induced dyskinesias and striatal cholinergic activity in patients with Parkinson's disease. Methods: This study included 13 Parkinson's disease patients with peak‐of‐dose levodopa‐induced dyskinesias, 12 nondyskinetic patients, and 12 healthy controls. Participants underwent 5‐[\(^{123}\)I]iodo‐3‐[2(S)‐2‐azetidinylmethoxy]pyridine single‐photon emission computed tomography, a marker of nicotinic acetylcholine receptors, [\(^{123}\)I]N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane single‐photon emission computed tomography, to measure dopamine reuptake transporter density and 2‐[\(^{18}\)F]fluoro‐2‐deoxyglucose positron emission tomography to assess regional cerebral metabolic activity. Striatal binding potentials, uptake values at basal ganglia structures, and correlations with clinical variables were analyzed. Results: Density of nicotinic acetylcholine receptors in the caudate nucleus of dyskinetic subjects was similar to that of healthy controls and significantly higher to that of nondyskinetic patients, in particular, contralaterally to the clinically most affected side. Interpretation: Our findings support the hypothesis that the expression of dyskinesia may be related to cholinergic neuronal excitability in a dopaminergic‐depleted striatum. Cholinergic signaling would play a role in maintaining striatal dopaminergic responsiveness, possibly defining disease phenotype and progression. KW - levodopa-induced dyskinesia KW - cholinergic activity KW - Parkinson’s disease Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170406 VL - 4 IS - 9 ER - TY - JOUR A1 - Palmisano, Chiara A1 - Brandt, Gregor A1 - Vissani, Matteo A1 - Pozzi, Nicoló G. A1 - Canessa, Andrea A1 - Brumberg, Joachim A1 - Marotta, Giorgio A1 - Volkmann, Jens A1 - Mazzoni, Alberto A1 - Pezzoli, Gianni A1 - Frigo, Carlo A. A1 - Isaias, Ioannis U. T1 - Gait Initiation in Parkinson’s Disease: Impact of Dopamine Depletion and Initial Stance Condition JF - Frontiers in Bioengineering and Biotechnology N2 - Postural instability, in particular at gait initiation (GI), and resulting falls are a major determinant of poor quality of life in subjects with Parkinson’s disease (PD). Still, the contribution of the basal ganglia and dopamine on the feedforward postural control associated with this motor task is poorly known. In addition, the influence of anthropometric measures (AM) and initial stance condition on GI has never been consistently assessed. The biomechanical resultants of anticipatory postural adjustments contributing to GI [imbalance (IMB), unloading (UNL), and stepping phase) were studied in 26 unmedicated subjects with idiopathic PD and in 27 healthy subjects. A subset of 13 patients was analyzed under standardized medication conditions and the striatal dopaminergic innervation was studied in 22 patients using FP-CIT and SPECT. People with PD showed a significant reduction in center of pressure (CoP) displacement and velocity during the IMB phase, reduced first step length and velocity, and decreased velocity and acceleration of the center of mass (CoM) at toe off of the stance foot. All these measurements correlated with the dopaminergic innervation of the putamen and substantially improved with levodopa. These results were not influenced by anthropometric parameters or by the initial stance condition. In contrast, most of the measurements of the UNL phase were influenced by the foot placement and did not correlate with putaminal dopaminergic innervation. Our results suggest a significant role of dopamine and the putamen particularly in the elaboration of the IMB phase of anticipatory postural adjustments and in the execution of the first step. The basal ganglia circuitry may contribute to defining the optimal referent body configuration for a proper initiation of gait and possibly gait adaptation to the environment. KW - gait initiation KW - Parkinson’s disease KW - basal ganglia KW - dopamine KW - base of support KW - anthropometric measurements Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200801 SN - 2296-4185 VL - 8 ER - TY - JOUR A1 - Canessa, Andrea A1 - Pozzi, Nicolò G. A1 - Arnulfo, Gabriele A1 - Brumberg, Joachim A1 - Reich, Martin M. A1 - Pezzoli, Gianni A1 - Ghilardi, Maria F. A1 - Matthies, Cordula A1 - Steigerwald, Frank A1 - Volkmann, Jens A1 - Isaias, Ioannis U. T1 - Striatal Dopaminergic Innervation Regulates Subthalamic Beta-Oscillations and Cortical-Subcortical Coupling during Movements: Preliminary Evidence in Subjects with Parkinson's Disease JF - Frontiers in Human Neuroscience N2 - Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson’s disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon computed tomography (SPECT) with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) to assess striatal dopaminergic innervation. Unilateral movement execution led to event-related desynchronization (ERD) followed by a rebound after movement termination event-related synchronization (ERS) of oscillatory beta activity in the STN and primary sensorimotor cortex of both hemispheres. Dopamine deficiency directly influenced movement-related beta-modulation, with greater beta-suppression in the most dopamine-depleted hemisphere for both ipsi- and contralateral hand movements. Cortical-subcortical, but not interhemispheric subcortical coherencies were modulated by movement and influenced by striatal dopaminergic innervation, being stronger in the most dopamine-depleted hemisphere. The data are consistent with a role of dopamine in shielding subcortical structures from an excessive cortical entrapment and cross-hemispheric coupling, thus allowing fine-tuning of movement. KW - beta oscillations KW - Parkinson’s disease KW - motor control KW - movement disorders KW - imaging KW - subthalamic nucleus KW - coherence analysis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164061 VL - 10 IS - 611 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Marcus, Charles A1 - Sheikhbahaei, Sara A1 - Solnes, Lilja B. A1 - Leal, Jeffrey P. A1 - Du, Yong A1 - Rowe, Steven P. A1 - Higuchi, Takahiro A1 - Buck, Andreas K. A1 - Lapa, Constantin A1 - Javadi, Mehrbod S. T1 - Visual and Semiquantitative Accuracy in Clinical Baseline 123I-Ioflupane SPECT/CT Imaging JF - Clinical Nuclear Medicine N2 - PURPOSE: We aimed to (a) elucidate the concordance of visual assessment of an initial I-ioflupane scan by a human interpreter with comparison to results using a fully automatic semiquantitative method and (b) to assess the accuracy compared to follow-up (f/u) diagnosis established by movement disorder specialists. METHODS: An initial I-ioflupane scan was performed in 382 patients with clinically uncertain Parkinsonian syndrome. An experienced reader performed a visual evaluation of all scans independently. The findings of the visual read were compared with semiquantitative evaluation. In addition, available f/u clinical diagnosis (serving as a reference standard) was compared with results of the human read and the software. RESULTS: When comparing the semiquantitative method with the visual assessment, discordance could be found in 25 (6.5%) of 382 of the cases for the experienced reader (ĸ = 0.868). The human observer indicated region of interest misalignment as the main reason for discordance. With neurology f/u serving as reference, the results of the reader revealed a slightly higher accuracy rate (87.7%, ĸ = 0.75) compared to semiquantification (86.2%, ĸ = 0.719, P < 0.001, respectively). No significant difference in the diagnostic performance of the visual read versus software-based assessment was found. CONCLUSIONS: In comparison with a fully automatic semiquantitative method in I-ioflupane interpretation, human assessment obtained an almost perfect agreement rate. However, compared to clinical established diagnosis serving as a reference, visual read seemed to be slightly more accurate as a solely software-based quantitative assessment. KW - Single-Photon-Emissions-Computertomographie KW - SPECT KW - Parkinson’s disease KW - Parkinsonism KW - DaTscan KW - 123I-Ioflupane KW - SPECT KW - SPECT/CT Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168181 SN - 1536-0229 VL - 44 IS - 1 ER -